Disease Progression in Multiple System Atrophy: The ASPIRE Multi-Modal Biomarker Study.

IF 7.7 1区医学 Q1 CLINICAL NEUROLOGY

Annals of Neurology Pub Date : 2025-08-26 DOI:10.1002/ana.70028

Margherita Fabbri, Natalia Del Campo, Wassilios G Meissner, Vanessa Rousseau, Agnès Sommet, Pierre Payoux, Pierre Gantet, Amel Drif, Hélène Catalá, Claire Thalamas, Christine Tranchant, Franck Durif, Ana Marques, Alexandre Eusebio, Luc Defebvre, Jean-Christophe Corvol, Stéphane Thobois, Anthime Flaus, Anne-Gaelle Corbille, Solène Frismand, Beverley Patterson, Alexandra Foubert-Samier, Anne Pavy-Le Traon, Germain Arribarat, Patrice Péran, Olivier Rascol

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引用次数: 0

Abstract

Objective: The objective of this study was to characterize changes in candidate biomarkers in early multiple system atrophy (MSA) and identify baseline predictors of faster progression.

Methods: This 1-year, multicenter, prospective study assessed clinical, neuroimaging (3T-magnetic resonance imaging [MRI], dopamine transporter single-photon emission computed tomography [DaT-SPECT]), and neurofilament light chain (NfL) changes in patients with early MSA (< 5 years from symptom onset) and healthy controls (HCs). Clinical and biomarker changes from baseline to 6 months (M6) and 12 months (M12) were analyzed. Survival status was collected at 24 months. Mixed linear regression analyzed repeated measures, whereas univariate regression identified biomarkers linked to progression. Sample size simulations were conducted for future trials.

Results: Forty-one patients with MSA and 20 HCs were included in this study. The Unified Multiple System Atrophy Rating Scale (UMSARS)-I + II scores worsened (mean percent change from baseline was 19.8% at M6; 95% confidence interval [CI] = 13.3 to 26.4% and 31.1% 95% CI = 24.9 to 37.2% at M12). Patients with MSA showed increased cerebellar white matter and pons atrophy (M6 = -5.9 to -2.8% and M12 = -9 to -4.9%) and decreased striatal specific binding ratio (SBR; M6 = -15.8 to -7.9% and M12 = -24 to -10.4%). Patients with multiple system atrophy parkinsonian (MSA-P) exhibited greater striatal SBR reduction, whereas patients with multiple system atrophy cerebellar (MSA-C) had greater cerebellar and pons atrophy, evident at M6. Baseline brainstem and pons volume predicted clinical worsening at M6, whereas SBR predicted worsening at M12. Higher plasma NfL levels correlated with early dropout (14% at M12), worse UMSARS scores, lower SBR, and increased mortality risk within 24 months.

Interpretation: Neuroimaging changes occur within 6 months in early MSA. High plasma NfL levels are linked to increased mortality and dropout risk. Longitudinal biomarker assessments provide valuable insights into disease progression. ANN NEUROL 2025.

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多系统萎缩的疾病进展：ASPIRE多模式生物标志物研究

目的：本研究的目的是表征早期多系统萎缩（MSA）候选生物标志物的变化，并确定更快进展的基线预测因素。方法：这项为期1年的多中心前瞻性研究评估了早期MSA患者的临床、神经影像学（3t磁共振成像[MRI]、多巴胺转运体单光子发射计算机断层扫描[DaT-SPECT]）和神经丝轻链（NfL）的变化（结果：41例MSA患者和20例hc患者纳入本研究）。统一多系统萎缩评定量表（UMSARS） i + II评分恶化（M6时与基线的平均百分比变化为19.8%；95%置信区间[CI] = 13.3至26.4%,31.1% 95% CI = 24.9至37.2%）。MSA患者表现为小脑白质增加，脑桥萎缩（M6 = -5.9 ~ -2.8%, M12 = -9 ~ -4.9%），纹状体特异性结合比降低（SBR; M6 = -15.8 ~ -7.9%, M12 = -24 ~ -10.4%）。多系统萎缩性帕金森病（MSA-P）患者纹状体SBR减少更大，而多系统萎缩性小脑（MSA-C）患者的小脑和脑桥萎缩更大，M6可见。基线脑干和脑桥体积预测M6期临床恶化，而SBR预测M12期恶化。较高的血浆NfL水平与早期辍学（M12时为14%）、较差的UMSARS评分、较低的SBR以及24个月内死亡风险增加相关。解释：早期MSA的神经影像学改变发生在6个月内。高血浆NfL水平与死亡率和辍学风险增加有关。纵向生物标志物评估为疾病进展提供了有价值的见解。Ann neurol 2025。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annals of Neurology 医学-临床神经学

CiteScore

18.00

自引率

1.80%

发文量

270

审稿时长

3-8 weeks

期刊介绍： Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.